Bastarrachea F
Departamento de Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, México, D.F., 04510, México.
J Theor Biol. 1998 Feb 21;190(4):379-87. doi: 10.1006/jtbi.1997.0563.
Many antibiotic resistance mutations arise in pathogenic bacteria that harbor plasmids (R-plasmids). Resistance to third generation cephalosporins, for instance, largely occurs by one or more point mutations in plasmid bla genes that expand the resistance spectrum of beta-lactamases. Here I review relevant evidence underlying the worldwide emergence of extended spectrum beta-lactamases (ESBLs). The conclusion reached is that the origin of these resistance-conferring mutations cannot be explained by a series of single point mutation and selection events. Instead, highly advantageous stochastic processes might exist that generate alterations in the sequence or the conformation of particular regions in chromosomal or plasmid genomes such as bla, i.e., recombination or mutation. Several explanations for the origin of ESBLs are reviewed but direct experimental evidence to support or to invalidate them is still lacking. The cellular conditions under which ESBLs arise are unknown; however, involvement of nutritional stresses inside natural animal hosts and of plasmid conjugal functions appear likely.
许多抗生素抗性突变出现在携带质粒（R质粒）的病原菌中。例如，对第三代头孢菌素的抗性很大程度上是由质粒bla基因中的一个或多个点突变引起的，这些突变扩展了β-内酰胺酶的抗性谱。在此，我回顾了超广谱β-内酰胺酶（ESBLs）在全球出现的相关证据。得出的结论是，这些赋予抗性的突变的起源不能用一系列单点突变和选择事件来解释。相反，可能存在高度有利的随机过程，这些过程会导致染色体或质粒基因组（如bla）中特定区域的序列或构象发生改变，即重组或突变。本文回顾了几种关于ESBLs起源的解释，但仍缺乏支持或否定这些解释的直接实验证据。ESBLs产生的细胞条件尚不清楚；然而，天然动物宿主内的营养应激和质粒接合功能的参与似乎是可能的。
